1. Field of the Invention
The present invention relates to a novel pharmaceutical composition comprising a solid dispersion of at least one active principle in a pharmaceutically acceptable polymer matrix comprising at least one continuous polydextrose phase and at least one continuous phase of a polymer other than polydextrose.
2. Description of the Art
Pharmaceutical compositions in the form of solid dispersions of active principles are well known to those skilled in the art. They are generally used to improve the solubility of active principles, to control their rate of release or to improve their bioavailability.
Many active principle molecules have a low bioavailability when taken orally. A low solubility in an aqueous medium (i.e. a solubility in water at 25° C. of less than 1 mg/ml), but also a poor permeability, may be responsible for their weak absorption after oral administration. Numerous techniques have been used in order to improve the bioavailability of these molecules when administered orally. This is the case of micronization, the formation of salts and complexes, solubilization in liquids and solid dispersions.
The concept of solid dispersions was introduced in 1961 by Sekiguchi and Obi (Chem. Pharm. Bull. 9, (1961), 866-872), and then taken up and defined by Goldberg in 1965 (J. Pharm. Sci. 54, (1965), 1145-1148) and Chiou and Riegelmann in 1971 (J. Pharm. Sci. 60(9), (1971) 1281-1302).
In general, the expression “solid dispersion” denotes a matrix in the solid state, as opposed to the liquid or gas state, comprising at least two constituents, the first of which, for example a pharmaceutical active principle, is dispersed as uniformly as possible within the other constituents, for example a pharmaceutically acceptable matrix. When the distribution consists of a single phase, such a “solid dispersion” will more particularly be called a “solid solution”: the dispersion takes place on a molecular scale, the active principle is then solubilized in the solid matrix and is in the amorphous state. When the solid solution is brought into contact with a liquid medium, such as the gastric medium, it can then readily form a liquid solution. When the distribution does not consist of a single phase, the expression “solid dispersion” is used: the dispersion takes place on a particulate scale (=50 nm). The active principle is either completely dispersed therein in the crystalline state, or partially solubilized therein.
There exists mainly two methods of preparing a “solid dispersion”:                the “solvent” approach, based on the solubilization of the components (active principle and matrix) in a common solvent, followed by evaporation of the solvent;        the “molten” approach which consists in melting the components (active principle and matrix) at high temperature and then in cooling the mixture in order to allow solidification.        
The “solvent” approach has many drawbacks: implementation is complex, there is in particular a multitude of steps related to the treatment of the solvents, resulting in a high cost, and also environmental and public health problems (residual contents of solvents).
The “molten” approach does not have such drawbacks, but requires the use of high temperatures that can affect the chemical stability of the active principles and of the other components of the solid dispersion.
The solid dispersions included in the pharmaceutical compositions of the prior art are, in general, formed from an active principle dissolved or dispersed in a matrix of one or more pharmaceutically acceptable polymer(s).
Patent applications EP 0 240 904 and EP 0 240 906 (BASF AG) thus describe a process for preparing solid pharmaceutical forms by means of an extrusion or injection-molding process, preferably using N-vinylpyrrolidone copolymers, in particular copovidone.
Nevertheless, the compositions of the prior art comprising solid dispersions do not always make it possible to obtain, in particular, a satisfactory increase in the bioavailability of relatively water-insoluble active principles, due to the very fact of this low solubility all along the gastrointestinal tract.
All of the references described herein are incorporated herein by reference in their entirety.